Diagnostic and prognostic relevance of serum miR-195 in pediatric acute myeloid leukemia

Abstract

BACKGROUND:

MicroRNA-195 acts as a tumor suppressor in a variety of cancers. However, its clinical significance in pediatric acute myeloid leukemia (AML) remains largely undefined.

OBJECTIVE:

To investigate the diagnostic and prognostic relevance of miR-195 in this malignancy.

METHODS:

Expression levels of miR-195 in peripheral blood and bone marrow samples of patients with pediatric AML and normal controls were detected by real-time quantitative PCR. Then, receiver-operating characteristic (ROC) curve analysis, Kaplan-Meier method, and Cox regression analysis were performed to evaluate the diagnostic and prognostic relevance of serum miR-195 in pediatric AML.

RESULTS:

Compared to normal controls, the expression levels of miR-195 in both bone marrow and patients’ sera were significantly decreased (both $P<$ 0.001). In addition, serum miR-195 had an optimal diagnostic cut-off point (2.09) for pediatric AML with sensitivity of 68.87% and specificity of 96.23%. The area under the ROC curve (AUC) based on serum miR-195 was 0.910. Moreover, patients with low serum miR-195 level more often had French-American-British classification subtype M7 ( $P=$ 0.02), unfavorable karyotypes ( $P=$ 0.01), and shorter relapse-free and overall survivals (both $P=$ 0.001) than those with high serum miR-195 level. Furthermore, the multivariate analysis identified serum miR-195 level as an independent prognostic factor for both relapse-free and overall survivals.

CONCLUSION:

The findings of this study suggest that the aberrant expression of miR-195 may play crucial roles in the development and progression of pediatric AML patients. Serum miR-195 may serve as a promising marker for monitoring the occurrence of this disease and predicting the clinical outcome of patients.

Keywords

Pediatric acute myeloid leukemia microRNA-195 serum real-time quantitative PCR prognosis

1. Introduction

Acute myeloid leukemia (AML) represent a heterogeneous group of clonal diseases arise from hematopo- ietic tissues due to malignant transformation of a bone marrow-derived, self-renewing stem cell or myeloid progenitor [2, 3]. AML is characterized by abnormal proliferation of progenitor cells of myeloid lineage, leading to the insufficient generation of normal mature blood cells [4]. AML contributes to about 25% of pediatric leukemia cases and accounts for approximately 30% of cancer-related deaths in this age range [5]. With the recent development of therapeutic strategies for this disease, such as chemotherapy and hematopoietic stem cell transplantation, the prognosis in patients with pediatric AML has improved and the long-term survival rate approaches 70% at this time [6]. Infections, bleeding episodes, leukostasis, and tumor lysis syndrome have been indicated to be the main causes of death, and disease relapse has been considered as the main cause affecting the mortality rate of patients with this disease [7]. Therefore, it is of great significance to identify novel prognostic factors and efficient risk-based post-remission therapeutic strategies for patients with pediatric AML.

MicroRNAs (miRNAs) is a class of small (with length in 18–26 nucleotides), non-coding, endogenous RNAs which regulate gene expression by directly binding to specific seed sequences in the 3’ untranslated region (UTR) of the corresponding target mRNAs [8]. MiRNAs were originally identified in C. elegans in 1993 [9]. With high conservation in mammals, miRNAs function as crucial regulators of various biological processes such as cell differentiation, growth, development, proliferation, and apoptosis [10]. Growing evidences show the involvement of miRNAs in a variety of human cancers and indicate that several miRNAs are widely deregulated in carcinogenesis and cancer progression [11]. Especially, a number of miRNAs have been reported to be involved into pediatric AML by recent studies [12]. For example, our previous findings indicated that the upregulation of miR-375 was one of the molecular mechanisms involved in the development and progression of pediatric AML, and this miRNA might function as an independent prognostic factor [13]; we reported the upregulation of miR-100 was significantly associated with poor relapse-free and overall survivals of patients with pediatric AML [14]; Our previous data also indicated that the downregulation of miR-29a was associated with advanced clinical features and poor prognosis of pediatric AML patients [15].

MiR-195, together with miR-15a, miR-15b, miR-16-1 and miR-16-2, belongs to the miR-15/16/195 family, and is localized in chromosome 17p13.1 [16]. The sequence of mature miR-195 is conserved across mammalian species [17]. Accumulating studies have indicated the roles of miR-195 in tumorigenesis and cancer therapy. The abnormal expression of miR-195 has been found in multiple cancer tissues, including breast cancer, lung cancer, hepatocellular carcinoma, gastric cancer, colorectal cancer, bladder cancer and prostate cancer [18, 19, 20, 21, 22, 23, 24]. Functionally, miR-195 has been demonstrated to act as a tumor suppressor during various cancer processes, including cancer cell proliferation, migration, invasion, apoptosis. However, its clinical significance in pediatric AML remains largely undefined. To address this problem, this study detected the expression levels of miR-195 in peripheral blood and bone marrow samples of patients with pediatric AML and healthy controls by real-time quantitative PCR. Then, receiver-operating characteristic (ROC) curve analysis, Kaplan-Meier method, and Cox regression analysis were performed to evaluate the diagnostic and prognostic relevance of serum miR-195 in pediatric AML.

2. Materials and methods

2.1 Patients and tissue samples

In this study, we used the same patient corhot with our previous studies [13, 14]. Our study was approved by Huai’an First People’s Hospital Ethics Committee. Prior informed consent was obtained from the patients for the collection of specimens in accordance with the guidelines of Huai’an First People’s Hospital, China. All specimens were handled and made anonymous according to the ethical and legal standards. The clinical characteristics of 106 patients with AML was summarized in Table 1.

Table 1
Association of serum miR-195 level with clinical characteristics of 106 pediatric acute myeloid leukemia patients

Clinical variables	No. of patients (%)	Serum miR-195 ( $n$ , %)		$P$
		Low	High
Gender
Male	58 (54.7)	29 (50.00)	29 (50.00)	NS
Female	48 (45.3)	26 (54.17)	22 (45.83)
Age (year)
$>$ 6	40 (37.7)	20 (50.00)	20 (50.00)	NS
$\leqslant$ 6	66 (62.3)	35 (53.03)	31 (46.97)
Leukocyte ( $\mu$ L)
$>$ 10,000	66 (62.3)	35 (53.03)	31 (46.97)	NS
$\leqslant$ 10,000	40 (37.7)	20 (50.00)	20 (50.00)
French-American-British classification
M0	3 (2.8)	0 (0)	3 (100.0)	0.02
M1/M2	62 (58.5)	23 (37.10)	39 (62.90)
M3	10 (9.4)	5 (50.00)	5 (50.00)
M4/M5	21 (19.8)	14 (66.67)	7 (33.33)
M7	10 (9.4)	9 (90.00)	1 (10.00)
Extramedullary disease
Absent	80 (75.5)	37 (46.25)	43 (53.75)	NS
Present	26 (24.5)	14 (53.85)	12 (46.15)
Cytogenetics
Favorable	35 (33.0)	8 (22.86)	27 (77.14)	0.01
Intermediate	52 (49.1)	25 (48.08)	27 (51.92)
Unfavorable	19 (17.9)	18 (94.74)	1 (5.26)
Day 7 response to treatment
Favorable	65 (61.3)	32 (49.23)	33 (50.77)	NS
Unfavorable	41 (38.7)	23 (56.10)	18 (43.90)

2.2 Real-time quantitative RT-PCR

Expression levels of miR-195 in bone marrow mon- onuclear cells and sera of patients with AML were detected by real-time quantitative RT-PCR according to the protocols described in our previous studies [13, 14]. RNU6B were used as an internal reference gene. The primer sequences were as following: for miR-195: forward 5’-GAT AGC AGC ACA GAA ATA TTG GC-3’, reverse 5’-ACA CGG ATA GTG TTG CTT GTC-3’; for RNU6B: forward 5’-CGC TTC GGC AGC ACA TAT AC-3’, reverse 5’-TTC ACG AAT TTG CGT GTC AT-3’. Relative quantification of target miRNA expression was evaluated using the comparative cycle threshold (CT) method. The raw data were presented as the relative quantity of target miRNA, normalized with respect to RNU6B. Each sample was examined in triplicate.

2.3 Statistical analysis

The software of SPSS version 11.0 for Windows (SPSS Inc, IL, USA) was used for all statistical analyses in the current study. Data were shown as mean $\pm$ standard deviation (SD). Group differences were compared using two-tailed Student’s $t$ test. The correlation of miR-195 expression between bone marrow mononuclear cells and patients’ sera was determined by Spearman Correlation analysis. ROC curve and the area under the ROC curve (AUC) were applied to evaluate the diagnostic value of serum miR-195 level in pediatric AML. Associations between serum miR-195 level and clinicopathological features of patients with pediatric AML were performed using the $\chi^{2}$ test for categorical variables. The Kaplan-Meier survival curves were used to determine any significant relationship between the serum level of miR-195 expression and the status of the patients with respect to relapse-free survival (RFS) or overall survival (OS). $P$ values less than 0.05 were considered to be statistically significant.

Table 2
Univariate analysis of the impact of variables on relapse-free survival and overall survival in pediatric AML patients

Variable	No. of patients	Relapse-free survival		Overall survival
		Median (months $\pm$ S.D.)	$P$	Median (months $\pm$ S.D.)	$P$
Cytogenetics
Favorable	35	Not reached	$<$ 0.001	Not reached	$<$ 0.001
Intermediate	52	12.61 $\pm$ 1.82		22.90 $\pm$ 2.12
Unfavorable	19	3.14 $\pm$ 0.53		9.81 $\pm$ 1.73
French-American-British classification
M1-M6	96	14.26 $\pm$ 2.19	0.01	36.26 $\pm$ 3.81	0.008
M7	10	7.92 $\pm$ 1.44		20.72 $\pm$ 2.52
MiR-195 expression
Low	55	5.68 $\pm$ 0.68	0.01	20.32 $\pm$ 1.26	0.01
High	51	10.92 $\pm$ 0.89		36.68 $\pm$ 2.82

Figure 1.

Decreased expression of miR-195 in patients with pediatric AML. (A) Compared to healthy controls, the expression levels of miR-195 were significantly decreased in bone marrow of patients with pediatric AML (AML vs. normal: 2.14 $\pm$ 0.81 vs. 3.53 $\pm$ 1.19, $P<$ 0.001); (B) Compared to healthy controls, the expression levels of miR-195 were significantly decreased in sera of patients with pediatric AML (AML vs. normal: 2.28 $\pm$ 1.04 vs. 3.98 $\pm$ 1.45, $P<$ 0.001); (C) The expression levels of miR-195 in the bone marrow of pediatric AML patients were closely correlated with those in patients’ sera (Spearman’s correlation: $r=$ 0.76, $P=$ 0.01); (D) Diagnostic value of serum miR-195 level in patients with pediatric AML. The AUC value was 0.910 ( $P=$ 0.0001; 95% CI, 0.863 to 0.945). At the optimal diagnostic cut-off point of serum miR-195 level was 2.09, the sensitivity was 68.87% (95% CI, 59.10–77.50%) and the specificity was 96.23% (95% CI, 90.60–98.90%).

3. Results

3.1 Decreased expression of miR-195 in patients with pediatric AML

Compared to healthy controls, the expression levels of miR-195 in both bone marrow and patients’ sera were significantly decreased (in bone marrow, AML vs. normal: 2.14 $\pm$ 0.81 vs. 3.53 $\pm$ 1.19, $P<$ 0.001, Fig. 1A; in serum, AML vs. normal: 2.28 $\pm$ 1.04 vs. 3.98 $\pm$ 1.45, $P<$ 0.001, Fig. 1B). More interestingly, the expression levels of miR-195 in the bone marrow of pediatric AML patients were closely correlated with those in patients’ sera (Spearman’s correlation: $r=$ 0.76, $P=$ 0.01, Fig. 1C). Thus, we investigated the clinical significance of miR-195 in pediatric AML patients using its serum levels in the next sections.

3.2 Diagnostic value of serum miR-195 level in patients with pediatric AML

Based on the expression levels of miR-195 in patients and healthy controls’ sera, ROC curve was drawn and AUC value was calculated to assess the diagnostic efficiency of serum miR-195 level in pediatric AML. As shown in Fig. 1D, the AUC value was 0.910 ( $P=$ 0.0001; 95% CI, 0.863 to 0.945). At the optimal diagnostic cut-off point of serum miR-195 level was 2.09, the sensitivity was 68.87% (95% CI, 59.10–77.50%) and the specificity was 96.23% (95% CI, 90.60–98.90%).

Table 3
Multivariate analysis of the impact of variables on relapse-free survival and overall survival in pediatric AML patients

Variable	$P$	Odds ratio	95% Confidence interval
Relapse-free survival
Cytogenetics
Unfavorable vs. Favorable/Intermediate	0.01	5.92	1.06–22.88
French-American-British classification
M7 vs. M1-M6	0.06	2.33	0.73–8.62
MiR-195 expression
High vs. Low	0.02	5.28	1.02–22.09
Overall survival
Cytogenetics
Unfavorable vs. Favorable/Intermediate	0.009	7.09	1.58–33.96
French-American-British classification
M7 vs. M1-M6	0.06	2.52	0.89–8.73
MiR-195 expression
High vs. Low	0.02	5.06	1.00–21.92

Figure 2.

Kaplan-Meier curves of relapse-free survival (RFS, A) and overall survival (OS, B) of patients with pediatric AML stratified by the serum miR-195 levels. Patients with low serum miR-195 levels had both shorter RFS and OS than those with high serum miR-195 levels (both $P=$ 0.001).

3.3 Low serum miR-195 level associates with aggressive clinical characteristics of patients with pediatric AML

To evaluate the associations of serum miR-195 levels with various clinical characteristics of patients with pediatric AML, all 106 patients with pediatric AML were divided into miR-195-low ( $n=$ 55) and miR-195-high ( $n=$ 51) expression groups using the median value of serum miR-195 level (1.76) in all 106 patients (ranged from 0.04 to 3.00) as a cutoff point. As shown in Table 1, the patients with low serum miR-195 level more frequently had French-American-British classification subtype M7 than those with high serum miR-195 level ( $P=$ 0.02, Table 1). In addition, the expression levels of miR-195 in pediatric AML patients’ sera with unfavorable karyotypes were lower than those with intermediate and favorable karyotypes ( $P=$ 0.01, Table 1). No significant associations between serum miR-195 level and patients’ gender and age, leukocyte count, extramedullary disease and day 7 response to treatment were found based on our statistical analysis (all $P>$ 0.05, Table 1).

3.4 Low serum miR-195 level associates with unfavorable clinical outcome of patients with pediatric AML

Kaplan-Meier curves in Fig. 2 indicated that pediatric AML patients with low miR-195 level had shorter RFS and OS than those with high miR-195 level (both $P=$ 0.001). In addition, univariate analysis found that RFS and OS of patients with pediatric AML were both significantly associated with the French-American-British classification subtype M7 ( $P=$ 0.01, Table 2), unfavorable cytogenetic abnormalities ( $P<$ 0.001, Table 2), and low miR-195 expression ( $P=$ 0.01, Table 2). Moreover, Cox proportional hazards multivariate analysis of the univariate predictors identified the cytogenetic abnormalities ( $P=$ 0.01 and 0.009, respectively) and the expression level of miR-195 (both $P=$ 0.02) as independent prognostic factors for RFS and OS (Table 3).

4. Discussion

MiRNAs are involved into the onset and development of multiple human cancer types. Since stable miRNAs have been found in biofluids, such as serum and plasma, the detection of cancer-related miRNAs is emerging as a non-invasive tool for cancer detection and monitoring. In the current study, we firstly identified the serum miR-195 level as a diagnostic marker of pediatric AML, and also demonstrated that the decreased expression of miR-195 was significantly associated with cancer progression and patients’ prognosis. These findings highlight the critical role of miR-195 in occurrence, progression and clinical outcome of patients with pediatric AML.

Growing evidence shows the roles of miR-195 in carcinogenesis, development, progression and cancer therapy. MiR-195 functions as a tumor suppressor via regulating the corresponding target genes involved into cancer cell proliferation, migration and invasion. For example, Díaz-Beyá et al. [25] reported that mir-195 targeted the RET proto-oncogene in AML with t (8; 16); Cai et al. [26] identified miR-195 as an independent prognostic factor for biochemical recurrence-free survival of patients with prostate cancer, and found that miR-195 inhibited cancer cell invasion and migration, and induced cancer cell apoptosis by targeting RPS6KB1; Du et al. [27] indicated that miR-195 could suppress the proliferation, migration and invasion of cervical cancer cells via the inhibition of CCND2 and MYB expression; Liu et al. [21] reported that miR-195 expression was lower in lung cancer tissues and was associated with poor survival outcome, and discovered that the overexpression of miR-195 suppressed tumor cell growth, migration and invasion; Wang et al. [28] revealed that low expression of miR-195 in hepatocellular carcinoma was associated with tumor size, portal vein thrombosis, TNM stage and patients’ survival; Zhao et al. [29] showed that miR-195 could inhibit cell proliferation in bladder cancer via inhibition of cell division control protein 42 homolog/signal transducer and activator of transcription-3 signaling; Wang et al. [23] reported that miR-195 might function as a key negative regulator of thyroid cancer progression by targeting Rafl. In line with these previous studies, the decreased expression of miR-195 in both bone marrow and patients’ sera of pediatric AML were found based on our data. We also found the diagnostic efficacy of serum miR-195 level for pediatric AML patients was satisfactory according to AUC curve, implying serum miR-195 level may be a sensitive tumor biomarker for diagnosing or monitoring this malignancy. Moreover, our statistical analysis verified that pediatric AML patients with French-American-British classification subtype M7 and unfavorable karyotypes had lower miR-195 levels in serum, which is consistent with existing evidences based on other cancers. More interestingly, miR-195 showed significant association with patients’ prognosis in survival curve, univariate and multivariate analyses. Reduced miR-195 level in serum was related to poor RFS and OS of pediatric AML patients.

In conclusion, our data suggest that the aberrant expression of miR-195 may play crucial roles in the development and progression of pediatric AML patients. Serum miR-195 may serve as a promising marker for monitoring the occurrence of this disease and predicting the clinical outcome of patients. However, there are two limitations in this study. At first, the intermediate cytogenetic risk group in our cohort is small in this moderate-sized pediatric sample. Secondly, the exact molecular mechanisms on the involvement of miR-195 dysregulation in pediatric AMLs need further more comprehensive investigations.

Footnotes

Conflict of interest

None.

References

Newman

and Liu

E.T.

, Perspective on BRCA1, Breast Disease 10 (1998), 3–10.

Lin

X.C.

Sun

G.P.

Wen

J.L.

Zhang

Y.M.

Yang

Z.G.

Zhang

H.T.

and Dai

, Molecular dysfunctions in acute myeloid leukemia revealed by integrated analysis of microRNA and transcription factor, Int J Oncol 48 (2016), 2367–2380.

Khushboo

and Kiran

, Acute lymphoblastic leukemia with normal platelet count, Cancer Translational Medicine 1 (2015), 168576.

Forthun

R.B.

Hinrichs

Dowling

T.H.

Bruserud

Ø.

and Selheim

, The past, present and future subclassification of patients with acute myeloid leukemia, Curr Pharm Biotechnol 17 (2016), 6–19.

Faulk

Gore

and Cooper

, Overview of therapy and strategies for optimizing outcomes in de novo pediatric acute myeloid leukemia, Paediatr Drugs 16 (2014), 213–227.

Schiller

G.J.

, Evolving treatment strategies in patients with high-risk acute myeloid leukemia, Leuk Lymphoma 55 (2014), 2438–2448.

Peloquin

G.L.

Chen

Y.B.

and Fathi

A.T.

, The evolving landscape in the therapy of acute myeloid leukemia, Protein Cell 4 (2013), 735–746.

Cohen

Burgos-Aceves

M.A.

and Smith

, Estrogen repression of microRNA as a potential cause of cancer, Biomed Pharmacother 78 (2016), 234–238.

Yang

Gao

Liu

Jin

Wang

and Li

, Competing endogenous RNA networks in human cancer: Hypothesis, validation, and perspectives, Oncotarget 7 (2016), 13479–13490.

10.

Rupaimoole

Calin

G.A.

Lopez-Berestein

and Sood

A.K.

, miRNA deregulation in cancer cells and the tumor microenvironment, Cancer Discov 6 (2016), 235–246.

11.

Kuninty

P.R.

Schnittert

Storm

and Prakash

, MicroRNA targeting to modulate tumor microenvironment, Front Oncol 6 (2016), 3.

12.

Yan

Sun

Lin

Zhang

Chen

and Shen

, MicroRNA biomarker identification for pediatric acute myeloid leukemia based on a novel bioinformatics model, Oncotarget 6 (2015), 26424–26436.

13.

Wang

Hong

Gao

and Feng

, Upregulation of microRNA-375 is associated with poor prognosis in pediatric acute myeloid leukemia, Mol Cell Biochem 383 (2013), 59–65.

14.

Bai

Guo

Hong

and Kuai

, Upregulation of microRNA-100 predicts poor prognosis in patients with pediatric acute myeloid leukemia, Onco Targets Ther 5 (2012), 213–219.

15.

Zhu

Wang

Kuai

Sun

Chen

and Hong

, Prognostic value of miR-29a expression in pediatric acute myeloid leukemia, Clin Biochem 46 (2013), 49–53.

16.

J.F.

Luo

Y.M.

Wan

X.H.

and Jiang

, Biogenesis of MiRNA-195 and its role in biogenesis, the cell cycle, and apoptosis, J Biochem Mol Toxicol 25 (2011), 404–408.

17.

Finnerty

J.R.

Wang

W.X.

Hébert

S.S.

Wilfred

B.R.

Mao

and Nelson

P.T.

, The miR-15/107 group of microRNA genes: Evolutionary biology, cellular functions, and roles in human diseases, J Mol Biol 402 (2010), 491–509.

18.

Wang

Zhang

Tong

and Qiu

, miR-195 is a key negative regulator of hepatocellular carcinoma metastasis by targeting FGF2 and VEGFA, Int J Clin Exp Pathol 8 (2015), 14110–14120.

19.

Almeida

M.I.

Silva

A.M.

Vasconcelos

D.M.

Almeida

C.R.

Caires

Pinto

M.T.

Calin

G.A.

Santos

S.G.

and Barbosa

M.A.

, miR-195 in human primary mesenchymal stromal/stem cells regulates proliferation, osteogenesis and paracrine effect on angiogenesis, Oncotarget 7 (2016), 7–22.

20.

Zhang

Wang

Guo

and Cui

, Serum miRNAs panel (miR-16-2*, miR-195, miR-2861, miR-497) as novel non-invasive biomarkers for detection of cervical cancer, Sci Rep 5 (2015), 17942.

21.

Liu

Guan

Wang

Chen

Zhang

Tao

Zhang

and Huang

, miR-195 inhibits EMT by targeting FGF2 in prostate cancer cells, PLoS One 10 (2015), e0144073.

22.

Singh

Yadav

Kumar

and Saini

, MicroRNA-195 inhibits proliferation, invasion and metastasis in breast cancer cells by targeting FASN, HMGCR, ACACA and CYP27B1, Sci Rep 5 (2015), 17454.

23.

Wang

Jiang

Sun

Yan

Wang

Liu

and Hu

, miR-195 is a key regulator of Raf1 in thyroid cancer, Onco Targets Ther 8 (2015), 3021–3028.

24.

Wang

and Cai

, MiR-195 inhibits the proliferation of human cervical cancer cells by directly targeting cyclin D1, Tumour Biol 37 (2016), 6457–6463.

25.

Díaz-Beyá

Navarro

Ferrer

Díaz

Gel

Camós

Pratcorona

Torrebadell

Rozman

Monzo

and Esteve

, Acute myeloid leukemia with translocation (8; 16)(p11; p13) and MYST3-CREBBP rearrangement harbors a distinctive microRNA signature targeting RET proto-oncogene, Leukemia 27 (2013), 595–603.

26.

Cai

Chen

Q.B.

Han

Z.D.

Zhang

Y.Q.

H.C.

Chen

J.H.

Chen

Y.R.

Yang

S.B.

Zeng

G.H.

Zhong

W.D.

and Wu

C.L.

, miR-195 inhibits tumor progression by targeting RPS6KB1 in human prostate cancer, Clin Cancer Res 21 (2015), 4922–4934.

27.

Lin

L.I.

Zhang

and Jiang

, microRNA-195 inhibits the proliferation, migration and invasion of cervical cancer cells via the inhibition of CCND2 and MYB expression, Oncol Lett 10 (2015), 2639–2643.

28.

Wang

Zhao

Fang

J.H.

Chen

M.X.

Yang

Jia

W.H.

Yuan

and Zhuang

S.M.

, MicroRNA-195 suppresses angiogenesis and metastasis of hepatocellular carcinoma by inhibiting the expression of VEGF, VAV2, and CDC42, Hepatology 58 (2013), 642–653.

29.

Zhao

Chen

Liu

Yan

Tong

and Zu

, microRNA-195 inhibits cell proliferation in bladder cancer via inhibition of cell division control protein 42 homolog/signal transducer and activator of transcription-3 signaling, Exp Ther Med 10 (2015), 1103–1108.

Diagnostic and prognostic relevance of serum miR-195 in pediatric acute myeloid leukemia

Abstract

BACKGROUND:

OBJECTIVE:

METHODS:

RESULTS:

CONCLUSION:

Keywords

1. Introduction

2. Materials and methods

2.1 Patients and tissue samples

Table 1 Association of serum miR-195 level with clinical characteristics of 106 pediatric acute myeloid leukemia patients

2.3 Statistical analysis

Table 2 Univariate analysis of the impact of variables on relapse-free survival and overall survival in pediatric AML patients

3.1 Decreased expression of miR-195 in patients with pediatric AML

3.2 Diagnostic value of serum miR-195 level in patients with pediatric AML

Table 3 Multivariate analysis of the impact of variables on relapse-free survival and overall survival in pediatric AML patients

3.4 Low serum miR-195 level associates with unfavorable clinical outcome of patients with pediatric AML

4. Discussion

Footnotes

Conflict of interest

References

Table 1
Association of serum miR-195 level with clinical characteristics of 106 pediatric acute myeloid leukemia patients

Table 2
Univariate analysis of the impact of variables on relapse-free survival and overall survival in pediatric AML patients

Table 3
Multivariate analysis of the impact of variables on relapse-free survival and overall survival in pediatric AML patients